Field of the Invention
This invention relates to methods and systems for studying age-related macular degeneration and further to methods for image analysis in an optical-coherence image.
Background
Presented below is background information on certain aspects of the present invention as they may relate to technical features referred to in the detailed description, but not necessarily described in detail. The discussion below should not be construed as an admission as to the relevance of the information to the claimed invention or the prior art effect of the material described.
Age-related macular degeneration (AMD) is the leading cause of irreversible severe vision loss in the developed world in individuals over the age of 65. AMD can manifest in its non-exudative form or in its more advanced exudative form, also known as dry AMD and wet AMD respectively. Dry AMD usually manifests without any symptoms of vision loss and always precedes the development of the more severe wet form. Early detection and prompt intervention in progressing cases of AMD have been shown to increase visual outcome, so it is crucial to identify signs of wet development at the earliest stage as possible. Once severe AMD fully develops, most treatments have sub-optimal visual outcomes; thus new approaches to identify patients at high risk for developing severe AMD to enable early detection of disease progression and protective intervention are critical.
Patients presenting with dry AMD can suddenly progress to wet AMD without any previous noticeable visual changes, and eye care professionals have currently no reliable method to tell if and when the dry form will turn into the more severe wet form. Considering the low incidence of patients progressing to the wet form (only about 10% of cases actually progress) severe AMD is usually detected once visual changes are irreversible. Successful and reliable prediction of AMD progression in the near future is a challenging problem that is unsolved to date.
Development of technology to accurately identify if a patient will develop wet AMD in the near term or in the longer term would be a major advance in AMD management since such technology would allow following patients according to how prone they are to progression to web AMD, permitting more frequent screening evaluation and potential earlier treatment of those patients or subjects with higher chances for AMD progression. This technology may also provide better biomarkers of AMD, enabling clinical drug trials for the treatment of dry AMD to prevent progression, by helping to evaluate the chances that a patient will develop AMD before and after receiving treatment.
Drusen are extracellular deposits that accumulate between the retinal pigment epithelium (RPE) and the inner collagenous layer of Bush's membrane, and they commonly appear with aging. Non-neovascular (dry) AMD is normally identified by a greater accumulation of drusen. Evaluation of color fundus photographs (CFPs) represents the current clinical practice standard for drusen assessment in dry AMD. It has been found that there is positive correlation in the number, size and extent of drusen observed in CFPs with risk of wet AMD progression in more than two years. In current clinical practice, patients presenting drusen in CFPs are diagnosed with dry AMD, and are later classified in three different progression risk categories (early, intermediate and advanced) according to drusen number, area and maximum size. These characteristics of drusen are usually estimated by visual inspection of CPFs with comparison to a set of standardized circles drawn either manually or semi-automatically. This classification is limited because it is very coarse (it can only identify a subgroup of patients with a maximum risk of progression or 8.8% over two years), and even patients classified with early dry AMD can suddenly turn into the wet form. Drusen can sometimes also be hard to identify in CPFs, and manual measurements are prone to human-induced errors and reader variability. Current assessment methods also do not take advantage of drusen volumetric properties (there is no depth resolution in CPFs) or the information obtained by quantitatively evaluating the changes drusen observed as AMD progresses over time. Current experimental AMD progression predictive methods include a combination of the afore-mentioned drusen classification in CPFs combined with genetic, demographic, and environmental factors such as smoking or diet. While these methods show promising results, they still not exploit a variety of quantitative features of drusen such as volumetric properties which may have a role in AMD progression.
Optical coherence tomography (OCT) is potentially highly valuable in providing imaging data useful for predicting AMD progress. OCT is an-vivo imaging method capable of resolving cross-sectional retinal substructures. In recent years, it has become a key diagnostic technology in the areas of retinal diseases and glaucoma, as well as among a diverse set of medical and surgical specialties, including gastroenterology, dermatology, cardiology, and oncology, among others. The technique was commercialized by Carl Zeiss Meditec, Inc. for inner retina imaging and is now considered superior to the current standard of care for the evaluation of a number of conditions. The more recently introduced Spectral Domain OCT (SD-OCT) allows very fast scanning (more than 20 000 axial scans per second) over a retinal area, with depth resolutions smaller than 5 μm, which makes possible three-dimensional visualization of high-resolution retinal substructure while minimizing artifacts due to patient movement or ocular contractions. SD-OCT is suitable for visualizing and quantifying the changes seen at different stages of AMD, because the RPE, the site of many of those pathological changes, is normally well visualized in OCT. Drusen normally appear in SD-OCT images as “bumps” in an otherwise smoothly curved RPE layer. SD-OCT enables the accurate identification of drusen and its depth differentiation allows quantification of their volumetric and reflective properties.
Previous studies indicate that there is a degenerative retinal process associated with the height of drusen observed in SD-OCT imaging. However, many other drusen characteristics have not been previously quantified via SD-OCT.